There are substantial data to suggest that altered cerebral connectivity is a key aspect of the neurobiology of autism. Nevertheless, the role of altered cerebral connectivity in the production of the core impairments of autism has is not yet fully understood. Of the impairments in autism, motor function is an excellent candidate for neurobiological study. Praxis abnormalities in particular are a robust and replicated finding in autism and have been well characterized behaviorally. Additionally, praxis behavior can be more easily quantified and experimentally controlled than can many aspects of complex communicative and social behavior. Praxis skill has been shown to correlate with clinical measures of communicative and social behavior. Further, the cerebral mechanisms that underlie praxis function are well understood. Specifically, inferior cortical parietal regions, premotor cortical regions and the connectivity between the two are known to be necessary for praxis function. The electroencephalogram (EEG) has been used successfully to study cerebral connectivity associated with praxis in adults with and without apraxia, however it has not yet been employed in children or in individuals with autism. The research proposed in the current application will address the role of altered cerebral connectivity in autism using EEG-based techniques and will relate these neurobiological alterations to impaired motor performance and impaired social and communicative performance. The specific aims are (1) to characterize the functional network subserving praxis in children, (2) to demonstrate alterations of cerebral connectivity in children with autism during performance of praxis tasks, and (3) to assess the relationship between altered cerebral connectivity and motor, social and communicative ability. This project is proposed as part of a career development plan for the PI, a child neurologist, to obtain training in advanced EEG signal analysis, study design and systems neuroscience. The Kennedy Krieger Institute and Johns Hopkins University have world-class Biomedical Engineering, Biostatistics and clinical departments that provide an exceptional environment to enable the PI to become an independent investigator studying brain-behavior relationships in autism and other neurodevelopmental disabilities. PUBLIC HEALTH RELEVANCE: One theory says that different areas of the brain do not communicate with each other effectively in children with autism. The goal of this study is to understand how communication between brain regions differs in children with autism compared with typically developing children. This knowledge will be critical in order to develop treatments that alter the way brain regions communicate. PUBLIC HEALTH RELEVANCE: Preterm birth is a major public health concern due to significant neurodevelopmental delays that result and attributed to white matter injury in the brain. There are no therapies available that promote recovery and repair. The goal of this project is to promote cellular, metabolic, physiologic and behavior recovery of white matter injury sequelae by enhancing specific signaling pathways of endogenous progenitor cells in the brain.